PEPTIDE PRINTER FOR HIGH-THROUGHPUT SCREENING

描述(申请者摘要)：我们将建造一种能够 通过原位合成产生包含至少1000个独特的阵列 在单一底物(玻片或薄膜)上的多肽。综合将是 通过使用喷墨技术连续微量分配氨基酸来完成。 我们的十通道打印头，有效速率为每秒400个斑点 通道，将允许在1分钟内打印4000个氨基酸斑点。 使用微尺度合成、洗涤、阻塞、去保护和耦合循环将 从目前宏观综合的一小时减少到不到半小时 一小时，从而产生每小时多于一个残基的合成速率。 在不到24小时的时间内就能合成出15聚体多肽。增加的 密度和合成时间的减少将导致成本更低、成本更高 比目前可用的密度更高的阵列。第一阶段展示了 微分散技术可用于合成高纯度的多肽。在第二阶段，我们 将建造一台原型打印机，能够合成阵列，至少具有 1000种不同的多肽。原型系统将用于合成 基于具有良好特性的蛋白质的多肽阵列。这些多肽阵列将 用于验证大规模阵列的综合。多肽阵列将 将在宝洁公司的药物发现研究中生产和评估。 建议的商业应用： 多肽库用于药物筛选/发现和免疫学研究 (用于诊断和蛋白质表位测绘的抗体)。多肽文库阵列也 一种定义包括所有受体-配体的蛋白质-蛋白质相互作用域的有效工具， 抗体-抗原相互作用。将使用带有可定制多肽的多肽库芯片 通过以上所有的方式。

DESCRIPTION (applicant's abstract): We will build a peptide "printer" capable of producing, by in situ synthesis, arrays containing at least 1000 unique peptides on a single substrate (glass slide or membrane). The synthesis will be performed by successively microdispensing amino acids using ink-jet technology. Our ten channel printheads, having effective rates of 400 spots per second per channel, will allow 4,000 amino acid spots to be printed in under 1 minute. Using micro-scale synthesis, wash, block, deprotect, and coupling cycles will be reduced from one hour for current macro-scale synthesis, to less than half an hour, thus yielding a synthesis rate of more than one residue per hour. Fifteen-mer peptides will be synthesized in less than 24 hours. The increased density and decreased synthesis time will result in less expensive, higher density arrays than are currently available. Phase I demonstrated that the micro-dispensing can be used to synthesize high purity peptides. In Phase II we will build a prototype printer capable of synthesizing arrays with at least 1000 different peptides. The prototype system will be used to synthesize peptide arrays based on well-characterized proteins. These peptide arrays will be used to validate the synthesis for a large-scale array. Peptide arrays will be produced and evaluated in Proctor & Gamble's drug discovery research. PROPOSED COMMERCIAL APPLICATION: Peptide libraries are used for drug screening/discovery and immunological research (antibodies for diagnostics and protein epitope mapping). Peptide libraries arrays are also an efficient tool for defining protein-protein interaction domains including all receptor-ligand, antibody-antigen interaction. A peptide library-chip with customizable peptide will be used by all of the above.